The mammalian embryo, due to its viviparous development and small blastomeres has been refractory to prospective cell lineage analyses. Using the mouse as a model system, new technology now permits us to illuminate cell lineages in situ and to construct fate maps of the mammalian embryo. Two methods are now available to determine the developmental fates of cells in situ in mouse embryos and thus achieve the specific aims of this research proposal. One method utilizes chimeras which are animals that have been derived from more than one zygote. Although a considerable amount of embryological information has been obtained using chimeras, until recently, a suitable genetic cell marker system has not been available to topographically visualize the deployment of the chimeric components in histologic sections of tissues. We have developed and successfully used an immunocytochemical procedure for identifying the genotypes of cells within chimeric tissues and, by examining the clonal distributions of cells during ontogeny of a tissue at several critical developmental stages, accurate fate maps of the tissue can be delineated. A second method consists of directly labelling embryonic cells by the microinjection of a tracer(horseradish peroxidase) that is revealed in the progeny of the injected cell at later developmental stages. This procedure has been used in cell lineage studies of inframmamalian species and we have recently adapted it to the mouse embryo. These two methods will be used to study the developmental fates of cells in embryonic, fetal, neonatal, and prepubertal stages. We are specifically interested in following cells during gastrulation of the primitive streak stage and in the morphogenesis of the cerebellar cortex and the gonad from tissue foundation to final structure. The information obtained from these studies will permit us to distinguish whether a cell's embryologic fate is dependent upon its heritage or its current environment. We can then approach the possible cellular or molecular mechanisms responsible for the control of cell differentiation and how phenotypic diversity is generated among cells with the same genotype.